Project Summary/Abstract This application proposes a doctoral research training program that focuses on determining whether genetic modifiers of cystic fibrosis (CF) related lung and GI disease also modify health-related quality of life (HRQOL) in those patients. Presented in this application are plans for additional coursework, seminars, presentations, and a comprehensive research strategy. The research training environment at Case Western Reserve University is ideal for such a project, providing a wealth of resources and support for this project involving both basic and behavioral sciences. This campus is home to an accomplished team of CF geneticists, nursing faculty with ongoing funding and strong programs of research in health-related quality of life, collaborative relationships with the robust CF Care Center at University Hospitals of Cleveland, and a dedicated molecular research laboratory housed in the School of Nursing. CF patients experience significant variation in their clinical course, caused in part by modifier genes. Development of new treatments targeting these modifiers has been largely unsuccessful due in part to incomplete outcome measurement. Furthermore, no data exist on whether current treatments or the loci they target have any effect on HRQOL in these patients. Therefore, the purpose of this project is to determine whether genetic modifiers of CF-related pulmonary and GI disease also modify HRQOL. Data from this project will facilitate more informed outcome measurement in future treatment development and identify, based on modifier genotype, those CF patients who are most at-risk for decreased HRQOL. To accomplish this, we propose the following specific aims: Aim 1: Quantify the health-related quality of life experienced by adult CF patients cared for at Rainbow Babies and Children's hospital in Cleveland, Ohio. Aim 2: Determine allele and genotype frequencies for AGTR2 and SLC26A9 within our study population. Aim 3: Determine whether the GWAS identified variants (near AGTR2 and SLC26A9) are associated with subdomains of health-related quality of life as identified in Aim 1. Using a cross-sectional design, we will recruit a sample of 136 CF patients from the CF Care Center at University Hospitals, Cleveland Medical Center. We will then use a cheek swab to genotype each patient for the variants listed above and administer a CF-specific HRQOL tool. Finally, we will determine whether a relationship exists between each HRQOL subdomain and each genotype. This project will be completed with support from the student's interdisciplinary mentorship team and the director of the CF Care Center at University Hospitals. Dr. Daly has established a strong program of research in HRQOL and Dr. Darrah has advanced knowledge in genetics and CF and will provide co-mentorship. Dr. Barnholtz-Sloan has also offered her support and will provide training and mentorship in biostatistics.